Long-Term Weight Gain in Patients Treated With Open-Label Olanzapine in Combination With Fluoxetine for Major Depressive Disorder

Scott W. Andersen, M.S.; David B. Clemow, Ph.D.; and Sara A. Corya, M.D.

Objective: Patients with major depressive disorder (MDD) treated with olanzapine in combination with fluoxetine (OFC) demonstrate robust improvement in their depressive symptoms. Treatment with olanzapine may impact a patient's weight; thus, long-term weight gain and potential predictors (e.g., age and gender) and correlates (e.g., cholesterol and glucose levels) of weight gain were investigated in OFC-treated patients with MDD.

Method: Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for MDD were included (N = 549) in the current analyses of this 76-week, open-label study (February 2000 to July 2002). Maximum, endpoint, and potentially clinically significant (PCS; > = 7% increase from baseline) weight gain; time to PCS weight gain; and predictors and correlates of weight change were assessed. Patients were treated once daily with oral olanzapine (6, 12, or 18 mg) plus fluoxetine (25, 50, or 75 mg) capsules. Statistical significance for all tests was based upon p < = .05.

Results: Mean baseline-to-endpoint weight change was 5.6 ± 6.6 kg (12.3 ± 14.6 lb). Weight gain plateaued by 52 weeks. Fifty-six percent of patients met criteria for PCS weight gain by 76 weeks, and the median time to PCS weight gain was 16 weeks. Low baseline body mass index (BMI), female gender, younger age, and increased fluoxetine dose were predictors of weight gain; olanzapine dose was not. Patients with early ( <= 6 weeks) rapid PCS weight gain were 4.6 times more likely to gain substantial ( >= 15%) weight long-term (weeks 7-76). Changes to endpoint in total cholesterol and systolic blood pressure values were positively correlated with weight change.

Conclusion: Long-term (76 weeks) OFC treatment may lead to a large percentage (56%) of patients meeting criteria for PCS weight gain ( >= 7%). The risk of weight gain may be significantly increased for OFC-treated patients who have a low BMI or who are female, younger, or taking high-dose fluoxetine. It is important that prescribers balance the risk of weight gain with the benefit of treatment for individual patients with depression.

(J Clin Psychiatry 2005;66:1468-1476)